Association of PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population

Rev Soc Bras Med Trop. 2023 Jul 24:56:e01042023. doi: 10.1590/0037-8682-0104-2023. eCollection 2023.

Abstract

Background: Autophagy can inhibit the survival of intracellular microorganisms including Mycobacterium tuberculosis (Mtb), and the PI3K/AKT/mTOR pathway plays a crucial role. This study investigated the association between PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms and pulmonary tuberculosis (PTB) susceptibility.

Methods: KEGG pathway and gene ontology (GO) databases were searched for genes belonging to the PI3K/AKT/mTOR and autophagy pathways. Thirty SNPs in nine genes were identified and tested for their associations with tuberculosis in 130 patients with PTB and 271 controls. We constructed genetic risk scores (GRSs) and divided the participants into 3 subgroups based on their GRSs:0-5, 6-10, and 11-16.

Results: This analysis revealed that the AKT1 (rs12432802), RPTOR (rs11654508, rs12602885, rs2090204, rs2589144, and rs2672897), and TSC2 (rs2074969) polymorphisms were significantly associated with PTB risk. A decreasing trend was observed (P trend 0.020), in which a lower GRS was associated with a higher risk of PTB ([6-10] vs. [0-5]: OR (95%CI) 0.590 (0.374-0.931); [11-16] vs. [0-5]: OR (95%CI) 0.381 (0.160-0.906)).

Conclusions: Polymorphisms in AKT1, RPTOR, and TSC2 may influence susceptibility to PTB.

MeSH terms

  • Autophagy* / genetics
  • Case-Control Studies
  • East Asian People
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Proto-Oncogene Proteins c-akt* / genetics
  • TOR Serine-Threonine Kinases / genetics
  • Tuberculosis, Pulmonary* / epidemiology
  • Tuberculosis, Pulmonary* / genetics

Substances

  • AKT1 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • RPTOR protein, human
  • TOR Serine-Threonine Kinases
  • TSC2 protein, human

Grants and funding

Financial Support: This work was supported by the Sanming project of Medicine in Shenzhen (grant number SZSM201603029), the Natural Science Foundation of Guangdong Province (grant number 2018A030313123), the Nanshan Science and Technology Innovation Bureau (grant number NS2022100) and the Key Disciplines of Medicine in Nanshan District.